Clinical Abortion Rate Research Articles

P-536 The comparison of luteal phase support in modified natural cycle-frozen embryo transfer in young patients with high quality embryos -vaginal versus vaginal and subcutaneous progesterone.

Abstract Study question Does adding subcutaneous progesterone to vaginal administration affect pregnancy outcomes in young patients undergoing modified natural-frozen embryo transfer (mNC-FTET) with top-good quality, single blastocyst ? Summary answer Adding subcutaneous progesterone supplementation to vaginal administration after frozen-thawed embryo transfer in modified natural cycles does not improve live birth rates. What is known already Vaginal progesterone supplementation during frozen-thawed embryo transfer in modified natural cycles during luteal phase may increase the rate of live birth rate and decrease the rate of miscarriage. Study design, size, duration 245 participants were included in this retrospective cohort study conducted at a single IVF center between November 2020and January 2022.The primary outcome was the live birth rate; secondary outcomes included pregnancy, clinical pregnancy and biochemical and clinical abortion rates. Participants/materials, setting, methods 245 women aged 20-35 years in mNC-FTET cycles with a single top-good quality blastocyst embryo transfer were included. Patients with fibroids, synechiae, recurrent implantation failure, recurrent pregnancy loss were excluded. After thawing embryos were evaluated for quality, hCG(Ovitrelle-Merck) triggered; 129 patients received 200 mg vaginal progesterone (Lutinus-Merck)(group I), while 116 received 200 mg. vaginal and 25 mg subcutaneous progesterone (Progestan-Dex-Kocak Pharma) (group II). The main outcome was live birth rate(LBR), secondary outcome was miscarriage rate. Main results and the role of chance Baseline demographics and background characteristics were similar in the study groups. The live birth rate in group I is 86 of 106 (66.6%) compared 74 of 116 (63.7%) in group II (odds ratio 1,135, 95% confidence interval [CI]: 0.670-0.922, P = 0.637). There were 106 pregnant patients out of 129 in group I (82.17%) and 93 pregnant patients out of 116 in group II (odds ratio 0.877, 95 CI: 0.462-1,666, P = 0.68). The clinical pregnancy rate is 95 out of 129 patients (73.6%) in group I and 90 out of 116 patients in group II (odds ratio of 0.807, 95% confidence interval [CI]: 0.449-1.45, P = 0.474). The rate of biochemical abortion in group II was 10 of 129 patients (7.75%) and 4 of 116 (3.45%) (odds ratio 2.35, 95 CI: 0.717–7.718, P = 0.687). The clinical abortion rate was 6 of 129 patients (4.6%) and 6 of 116 patients (5.17%) in group II (odds ratio 2.35, 95 CI: 0.717-7.718; P = 0.687). According to primary and secondary outcomes, there were no significant differences between the groups. Limitations, reasons for caution To avoid bias, patients older than 35 years were excluded. Subcutaneous progesterone may be beneficial for older patients undergoing euploid embryo transfer. To reduce confounding factors, the number of patients was limited. Wider implications of the findings For luteal phase support, both vaginal and subcutaneous progesterone supplementation did not increase live birth rates following frozen-thawed embryo transfer in modified natural cycles in young patients. Trial registration number not applicable

P-523 rs2277698 Single nucleotides polymorphisms in tissue inhibitors of metalloproteinases 2 (TIMP2) affected clinical outcomes of women undergoing in vitro fertilization

Abstract Study question Is there any association between clinical outcomes of women undergoing in vitro fertilization (IVF) and the polymorphic variants of matrix metalloproteinases (MMPs) or tissue inhibitors of metalloproteinases (TIMPs)? Summary answer Our findings suggested that clinical outcomes of women undergoing IVF were associated with rs2277698 SNPs in TIMP2. What is known already The extracellular matrix proteolytic machinery is one of the most important mechanisms for regulating trophoblast invasion. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which are involved in the extracellular matrix proteolysis process, have the ability to regulate the degradation of the extracellular matrix and play a critical role in trophoblast invasion. Study design, size, duration A prospective study was composed of 1014 women undergoing their first fresh IVF cycle with non-donor from January 2014 to December 2015. Participants/materials, setting, methods The present study was carried out in Lee Women’s Hospital, Taiwan. DNA was extracted from the peripheral blood of all participants, and the SNPs were genotyped by real-time polymerase chain reaction. The effects of the following three single nucleotide polymorphisms (SNPs) on IVF outcomes were explored: TIMP1 (rs4898 C/T), TIMP2 (rs2277698 C/T) and MMP2 (rs243865 C/T). The SNP genotype, correlation with clinical pregnancy, embryo implantation, abortion and live birth rates of IVF were analyzed. Main results and the role of chance In the analysis of 1014 patients attempting their first cycle of IVF, the genotypes frequencies of the study population showed a statistically significant association between TIMP2 (rs2277698 C/T) and clinical outcome. For TIMP2 polymorphisms, women with wild genotype (CC) hadhigher clinical pregnancy rate (34.8% v.s 28.0%; p = 0.032), embryo implantation rate (19.4% v.s 15.4%; p = 0.009), live birth rate (29.8% v.s 22.1%; p = 0.006), and lower abortion rate (7.0% v.s 17.1%; p = 0.005) compared women with CT/TT genotype. On the other hand, the clinical outcomes in different TIMP1 or MMP2 gene polymorphisms groups were no statistically significant difference. Limitations, reasons for caution The size number of the study samples. Wider implications of the findings This study showed that the TIMP2 SNP polymorphisms CT/TT was associated with low trend of clinical outcomes. The mechanism of TIMP2 gene T allele affected the outcomes of IVF remains to be determined. Further studies should focus on the mechanism of these associations in a larger, more heterogeneous cohort. Trial registration number CS13194

Single-Dose Versus Multiple-Dose GnRH Agonist for Luteal-Phase Support in Women Undergoing IVF/ICSI Cycles: A Network Meta-Analysis of Randomized Controlled Trials.

BackgroundAlthough gonadotropin-releasing hormone (GnRH) agonist has been introduced as a beneficial luteal phase support (LPS), the optimal strategy of GnRH agonist remains unclear. This network meta-analysis was therefore performed to determine the comparative efficacy and safety of multiple-dose versus single-dose GnRH agonist protocol for LPS in patients undergoing IVF/ICSI cycles.MethodsWe searched relevant studies in PubMed, Embase and the Cochrane Registry of Controlled Trials (CENTRAL) from their inception util to September 2021. Live birth, clinical pregnancy rate, multiple pregnancy rate, and clinical abortion rate was evaluated. Pairwise and network meta-analysis were conducted using RevMan and ADDIS based on random-effects model, respectively. Moreover, the prioritization of protocols based on ranking probabilities for different outcomes were performed.ResultsSixteen RCTs met our eligibility criteria. Pairwise meta-analysis showed that multiple-dose protocol of GnRH agonist was effective for increasing live birth rate (OR 1.80, 95% CI 1.15 to 2.83, p=0.01) and clinical pregnancy rate (OR 1.89, 95% CI 1.01 to 3.56, p=0.05) as well as decreasing clinical abortion rate (OR 0.55, 95% CI 0.34 to 0.90, p=0.02). Meanwhile, single-dose protocol of GnRH agonist was effective for increasing clinical pregnancy rate (OR 1.45, 95% CI 1.11 to 1.89, p=0.007) and multiple pregnancy rate (OR 2.55, 95% CI 1.12 to 5.78, p=0.03). However, network meta-analysis only confirmed that multiple-dose protocol of GnRH agonist was the best efficacious strategy for live birth rate (OR 2.04, 95% CrI 1.19 to 3.93) and clinical pregnancy rate (OR 2.10, 95% CrI 1.26 to 3.54).ConclusionBased on the results of NMA, multiple-dose protocol may be the optimal strategy for patients undergoing IVF/ICSI cycles owing to its advantage in increasing live birth and clinical pregnancy rate. Moreover, single-dose protocol may be the optimal strategy for improving multiple pregnancy rate. However, with the limitations, more RCTs are required to confirm our findings.

P–169 Does increasing the time interval between Oocyte-Retrieval and Oocyte-Denudation improve the results in ICSI cycles ?

Abstract Study question What should be the optimal time interval which elapses between oocyte retrieval and denudation followed by ICSI , for optimal results in ART cycles ? Summary answer Our study suggests that an optimum interval between oocyte retrieval and oocyte denudation followed by ICSI, leads to better results in ART cycles. What is known already It is widely accepted that the best timing for OPU is 34–39 hours after ovulation trigger. Some studies suggest that preincubation time before ICSI can be beneficial when it comes to fertilization and pregnancy rates while late ICSI (fertilization) may have negative results due to oocyte ageing. Other studies claim that there is no significant difference in ART results when ICSI is performed between 2–6 hours post Oocyte-Retrieval (OR) . Few studies state that 1–3 hours of COC-culture prior to denudation and oocyte injection is better as far as fertilization , embryo quality and improved oocyte cytoplasmic maturity is concerned. Study design, size, duration RCT of 234 ICSI cycles was carried out between 2017–2019. Patients were divided into two groups-: A- Early denudation with ICSI and B- Late denudation with ICSI.Both the groups were comparable in terms of female age, number of oocytes, day of transfer, number of embryos transferred and embryo quality. Fresh or frozen embryos were transferred , which were always derived from the same stimulation cycle. Exclusion criteria were : Severe male factor / TESA / PESA. Participants/materials, setting, methods 234 ICSI cycles with similar ovarian stimulation protocols were analyzed as per time range between triggering, OPU, denudation and ICSI. Patients were divided into two groups: A- Early denudation (1–2 hours after OPU) with ICSI (1–2 hours after denudation) and B- Late denudation (4–6 hours after Oocyte-Retrieval ) with ICSI (1–2 hours after denudation).Primary outcomes were oocyte maturation and fertilization rates and secondary outcomes were clinical pregnancy rate and abortion rates. Main results and the role of chance In group B ( Late denudation and ICSI), the mean fertilization rate was 67% and the Clinical Pregnancy rate was 46%. This was better than the mean fertilization rate of 56% and clinical pregnancy rate of 39% observed in group A ( Early denudation and ICSI). However the difference was not statistically significant. Therefore, ideal maturation rates were observed when denudation ( followed by ICSI ) was delayed and done 4–6 hours after Oocyte-Retrieval. In ICSI cycles in ART , ovarian stimulation is used to induce the simultaneous growth of multiple follicles, followed by final maturation and ovulation triggering with exogenous hCG. or GnRH-Agonist or both. Generally, oocyte retrieval (OR) is performed 34 - 36h later. In addition, 2–4 hours in culture of the cumulus oocyte complexes (COC) prior to oocyte injection is believed beneficial for fertilization and embryo quality, probably due to improved oocyte cytoplasmic maturity. However, in large ART centers with high workloads, following such definite time intervals is frequently very difficult. Limitations, reasons for caution In large busy centers , maintaining meticulous time intervals is difficult . As our study numbers are small, larger multicentric trials are required in order to confirm our findings and to provide more robust data . This data cannot be applied to IVM, TESE / PESE and severe male-factor infertility. Wider implications of the findings: To achieve a successful fertilization, both nuclear and cytoplasmic maturity are required. Our Study indicates that a slight delay in denudation following Oocyte-Retrieval , will yield a higher number of good quality oocytes. A higher success rate can also be expected due to more number of embryos available for transfer. Trial registration number Not applicable

Effect of Endometrial Thickness and duration of Estrogen Supplementation on In Vitro Fertilization-Intracytoplasmic Sperm Injection Outcomes in Fresh Ovum/Embryo Donation Cycles.

Background:There is no consensus regarding optimal endometrial thickness and duration of estrogen supplementation in embryo transfer cycles, at present.Aims:To observe the effect of endometrial thickness and/or duration of estrogen supplementation on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in fresh ovum/embryo donation cycles.Settings and Design:This was a retrospective observational study. The study was conducted from January 2015 to November 2017.Subjects and Methods:Nine hundred and fifty seven fresh blastocyst transfer cycles in the recipients of oocyte/embryo donation regardless of reproductive history and diagnosis conducted at Nova IVF Fertility, Ahmedabad, Gujarat, India. Of these, 315 women had single embryo transfer (SET), while 642 had double embryo transfer (DET). Only fresh blastocysts derived from oocytes of young donors (≤30 years) and transferred in a uniform hormone replacement therapy (HRT) cycle were included. The effect of endometrial thickness and duration of estrogen on live birth rate (LBR) and other IVF/ICSI outcomes were analyzed.Statistical Analysis:Univariate logistic regression.Results:A significant improvement in LBR was noted in the recipients with each millimeter increase in endometrial thickness starting from 6 mm after transfer of either single (odds ratio [OR] = 1.3, P = 0.003) or double (OR = 1.14, P = 0.0218) blastocysts. Lower LBR was observed in recipients having SET and who received estrogen supplementation of <10 days (OR = 0.72; P = 0.02). Implantation rate and clinical pregnancy rate also improved significantly with endometrial thickness, but there was no change in clinical abortion rate and ectopic pregnancy rate.Conclusions:After minimizing the possible oocyte factor by including only donor oocytes and that of COH using a uniform HRT protocol, LBR improved with each millimeter increase in endometrial thickness starting from 6 mm. Shorter duration of estrogen supplementation (<10 days) reduced the chances of live birth in recipients after transfer of a single blastocyst.

The effect of intrauterine insemination preceding frozen-thawed elective single embryo transfer in couples with unexplained subfertility.

This prospective randomized controlled trial aimed to evaluate the effect of intrauterine insemination (IUI) before frozen-thawed elective single embryo transfer (FT-eSET). A total of 200 couples with unexplained subfertility underwent in-vitro fertilization (IVF) treatment. Patients were randomly assigned to either FT-eSET or IUI preceding FT-eSET. Both groups were composed of 100 women. IUI was timed 6 days before FT-eSET in the IUI preceding FT-eSET group. Implantation rates (IR), biochemical and clinical abortion rates (AR), clinical pregnancy rates (PR), ongoing pregnancy rates (PRs), and live birth rates were measured in this study. The IUI preceding FT-eSET group was associated with higher rates of clinical pregnancy, 54% vs. 42%, but not significantly. Similarly, IR, PR and live birth rate were higher in the IUI preceding FT-eSET group but not significantly. In the IUI preceding FT-eSET group, the biochemical and clinical abortion rates were lower than in the control group (9.5% vs. 14.2% and 5.5% vs. 5.2%, respectively). However, no statistically significant difference was found between the two groups, either. This is the first study showing that IUI may precede FT-eSET to improve PR in couples with unexplained subfertility. Also, performing IUI before FT-eSET may decrease biochemical and clinical abortion rates.

Uterine cavity assessment prior to IVF: comparison of 2D, 3D ultrasound, and hysteroscopy

There is a conflicting evidence that prior hysteroscopy in IVF treatment is beneficial in terms of successful pregnancy rate and subsequent live birth rate. So a study was planned to compare 2D TVS & 3D USG in detecting uterine anomalies in infertile patients & to know whether prior hysteroscopy has any effect on Clinical Pregnancy and Abortion rate. A sample size of 90 was selected and further randomized into 3 groups. Patients were randomized over 6-month time. All patients underwent same baseline investigations. In group 1 subjects, 2D TVS was done to detect uterine anomalies, in group 2 3D USG was performed and group 3 subjects underwent gold standard diagnostic hysteroscopy. Subjects in group 1 & 2 who tested positive for uterine anomalies were confirmed with diagnostic hysteroscopy and subsequently excluded from the study. Those subjects who had false positive results in group 1 & 2 were included in group 3 for Frozen Embryo transfer. This procedure was done till each of the 3 groups had 30 subjects. Furthermore, subjects in group 1 & 2 who tested negative for uterine anomalies, underwent IVF but did not conceive further underwent diagnostic hysteroscopy to confirm the diagnosis as a part of calculating Sensitivity and Specificity of 2D TVS and 3D USG. A total of 160 patients were accessed and finally 90 were included in the study. There was no significant difference in baseline demographic characteristics, type of infertility, duration of infertility, hormonal profile & mean antral follicle count and size. The Sn, Sp, PPV for 2D TVS & 3D USG was found to be 66.6%, 90%, 75% & 90.9%, 95% and 90.9% respectively. There was no difference in CPR and miscarriage rate in patients who conceived in each group. The results of the study are in line with the previous studies. Larger scale RCTs need to be conducted to ascertain the exact role of prior hysteroscopy in pregnancy outcome in infertile patients with no uterine anomalies.

Long-term cryostorage of semen in a human sperm bank does not affect clinical outcomes

To evaluate the affect of the duration of donor sperm storage on pregnancy success among women undergoing assisted reproduction. Retrospective cross-sectional study. Sperm bank. A total of 119,558 specimens retrieved using a clinical information database of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from 2001 to2016. Analysis of semen samples and clinical outcomes after semen use. Clinical information included semen parameters before and after freezing, clinical pregnancy, abortion and live birth rates after semen use. The sperm's frozen-thaw survival rate decreased from 85.72% to 73.98% after 15years of cryopreservation (P<.01). The clinical pregnancy rate of women undergoing artificial insemination with donor sperm was 23.09%, 22.36% and 22.32%, the clinical abortion rate was 10.06%, 10.02% and 12.00% and the live birth rate was 82.17%, 80.21% and 80.00% in the groups with 0.5-5, 6-10 and 11-15 storage years, respectively. The clinical pregnancy rate of women undergoing invitro fertilization was 64.29%, 64.94% and 53.48%, the clinical abortion rate was 12.26%, 11.38% and 17.39% and the live birth rate was 81.63%, 79.11% and 73.91%, in the groups with 0.5-5, 6-10 and 11-15years, respectively. The long-term cryostorage of semen in a human sperm bank does not affect clinical outcomes. However, cryopreservation longer than 5years negatively influenced the quality of frozen-thawed donor sperm samples.

Effect of Body Mass Index on the Outcome of In-Vitro Fertilization/Intracytoplasmic Sperm Injection in Women.

Background:Obesity, a known epidemic, is a leading cause of various reproductive disorders. Association of body mass index (BMI) with pregnancy outcomes, either ovarian or endometrial, is controversial and least elucidated.Aim:This study aimed to analyze the effect of BMI on in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome in women using self-oocytes, embryos prepared from donor oocytes (DE), or vitrified/frozen embryos (VE) obtained from both the SE and DE groups.Materials and Methods:A 9-month retrospective study was conducted on women undergoing IVF/ICSI. The women were grouped according to the World Health Organization classification of BMI (<18.50, 18.50–24.99, 25.00–29.99, and ≥30.00 kg/m2). They were further subcategorized as SE, DE, and VE groups. Ongoing pregnancy rate (OPR) was recorded as primary, whereas pregnancy rate (PR), clinical PR (CPR), implantation rate (IR), and clinical abortion rate (CAR) were secondary endpoints. Age, number of mature eggs, usable embryos, and embryos transferred were also measured. The data were statistically analyzed using chi-square and analysis of variance. P-value <0.05 was considered statistically significant.Results:OPR was statistically insignificant across all the groups. Secondary outcomes were statistically insignificant in all the groups except in VE, where IR (P = 0.008) and CAR (P = 0.0002) were statically significant. Other parameters were statistically insignificant among all the groups. However, in the SE and VE groups, the mean age was statistically significant (SE, P = 0.0001; VE, P = 0.0191).Conclusion:This study showed marginal/no effect of BMI on oocyte quality/endometrial receptivity and, subsequently, on the pregnancy outcome. However, well-designed, larger prospective studies are needed to clarify the role of BMI in pregnancy outcome in women undergoing IVF/ICSI.

Efficacy of hyaluronan-rich transfer medium on implantation and pregnancy rates in fresh and frozen-thawed blastocyst transfers in Korean women with previous implantation failure.

ObjectiveTo evaluate the effect of hyaluronan-rich transfer medium on pregnancy and implantation rates in fresh and frozen-thawed embryo transfers in Korean women with previous implantation failure.MethodsThis retrospective study included 283 blastocyst transfers in patients with previous embryo transfer failure at a private fertility clinic. In the study group (n=88), blastocyst transfers were performed using an hyaluronan-rich transfer medium prior to transfer, whereas blastocyst transfers without any treatment served as controls (n=195). According to the type of transfer (fresh elective or frozen-thawed), all the blastocyst transfers were divided into two study and two control groups.ResultsThe patient's mean age, serum anti-Müllerian hormone level, causes of infertility, embryo quality, and the number of transferred embryos were comparable between the study and control groups. There were no significant differences in clinical pregnancy rate (45.5% vs. 43.1%), implantation rate (28.9% vs. 28.8%), and clinical abortion rate (10.0% vs. 8.3%) between the two groups, and these findings were not changed after subgroup analysis according to the type of transfer.ConclusionThe use of hyaluronan-rich transfer medium in the blastocyst transfer does not appear to have any significant effect on the implantation and pregnancy rates in patients with previous implantation failure.

Meta-analysis of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperm injection

To evaluate whether the addition of E(2) for luteal phase support (LPS) in IVF/intracytoplasmic sperm injection (ICSI) could improve the outcome of clinical pregnancy. Meta-analysis. University hospital center. Women underwent IVF or ICSI using the GnRH agonist or GnRH antagonist protocol. Progesterone alone or combined with E(2) for LPS. Clinical pregnancy rate per patient (CPR/PA), clinical pregnancy rate per ET, implantation rate, ongoing pregnancy rate per patient, clinical abortion rate, and ectopic pregnancy rate. Fifteen relevant randomized controlled trials (RCTs) were identified that included a total of 2,406 patients. There was no statistical difference between E(2) + P group and P-only group regarding the primary outcome of CPR/PA for different routes of administration of E(2) (oral, vaginal, and transdermal) or other relevant outcome measures. No significant effect was observed for different daily doses of E(2) (6, 4, and 2 mg), even through oral medication in CPR/PA. The best available evidence suggests that E(2) addition during the luteal phase does not improve IVF/ICSI outcomes through oral medication, even with different daily doses. Furthermore, RCTs that study other administration routes are needed.

Efficacy of cryopreservation of embryos generated by intracytoplasmic sperm injection with spermatozoa from frozen testicular tissue.

To evaluate the viability of frozen embryos generated by intracytoplasmic sperm injection (ICSI) with frozen testicular spermatozoa. A total of 68 fresh embryo transfer (ET) cycles and 85 subsequent frozen-thawed ET (FET) cycles were grouped according to the source of spermatozoa: fresh testicular spermatozoa (TESE) or frozen-thawed testicular spermatozoa (t-TESE). There were no significant differences in the age of female patients, number of oocytes, or fertilization rates in fresh ET cycles with TESE (TESE-fresh ET) versus t-TESE (t-TESE-fresh ET). The rate of embryo survival after thawing (95.7 % vs. 94.0 %) was similar in frozen ET cycles (FET) with TESE (TESE-FET) and with t-TESE (t-TESE-FET). While there were significant differences in the proportion of good quality embryos, no statistical differences were found in the pregnancy or clinical abortion rates between the two groups. Moreover, delivery rates were not significantly different. Although the proportion of good quality embryos was affected by cryopreservation of testicular tissue, embryo survival rate was not. As well, subsequent pregnancy could be achieved successfully via t-TESE-FET cycles. Therefore, FET is not affected by the cryopreservation of testicular tissue, and avoids further oocyte retrieval and TESE procedures.

Influence of the human sperm abnormalities on conventional in-vitro fertilization therapy outcome

Objective To observe the influence of the sperm abnormalities on conventional invitro fertilization therapy outcome. Methods Sperm of 105 infertile husband's semen was analyzed. The patients were divided into three groups according to the sperm morphology observed Using Kruger 's criteria: normal sperm morphology group (sperm normal morphology ≥ 15 % ), mild sperm abnormalities group( sperm normal morphology 10%- 15%), middle sperm abnormalities group (sperm normal morphology 5 % - 10 % ). Fertilization rate, cleavage rate, good quality embryo rate, implantation rate, clinical pregnancy rate and abortion rates were compared to study the influence of the sperm abnormalities on conventional IVF outcome. Results ①Fertilization rate(79.4 % vs 78.3 % ), cleavage rate(104. 6% vs98. 6%), good quality embryo rate(58. 1% vs 53. 9%), implantation rate (31.7% vs 30. 8%), clinical pregnancy rate(48.1% vs 42. 3%)and abortion rates(13.0% vs 18. 2%)were not significantly different between normal sperm morphology group and mild sperm abnormalities group(P>0. 05). ②The fertilization rate (79.4% vs 63.9%), good quality embryo rate(58. 14% vs 48.23%), implantation rate (31.7% vs 16. 7%) and clinical pregnancy rate(48.1%vs24.0%) of the normal sperm morphology group were higher than middle sperm abnormalities group(P 0. 05). ③The fertilization rate (78.3% vs 63.9%), good quality embryo rate (53. 9%vs 48. 2%) of the mild sperm morphology group were higher than middle sperm abnormalities group(P 0. 05). Conclusions There is a significant influence of middle sperm abnormalities on IVF fertilization rate, good quality embryo rate, implantation rate and clinical pregnancy rate. However, it could not be influenced on mild sperm abnormalities. Key words: Spermatozoa; Abnormalities; Insemination, artificial

Hyaluronan-enriched transfer medium in cleavage-stage frozen-thawed embryo transfers increases implantation rate without improvement of delivery rate

To investigate the efficacy of hyaluronan-enriched transfer media in cleavage-stage frozen embryo transfer cycles. Two commercially available transfer media were prospectively compared in an observational study. Hospital-based in vitro fertilization clinic. Patients (n = 425) undergoing frozen-thawed embryo transfer (FET). The embryos transferred were included in either a study group (high hyaluronic acid [HA], n = 199) or a control group (low HA, n = 226). Delivery rate per FET; positive hCG rate, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, and clinical abortion rate were secondary outcomes. The use of HA in the transfer media significantly increased the positive hCG rate (37.2% vs. 25.2%) and implantation rate (23.1% vs. 15.8%) without increasing the delivery rate (21.6% vs. 21.2%). More subjects in the study group with a positive hCG test experienced biochemical pregnancy (28.4% vs. 8.9%). Addition of HA to transfer media seems to favor attachment of early embryos in FETs without increasing the delivery rate.

Effects of estradiol supplementation during the luteal phase of in vitro fertilization cycles: a meta-analysis

To clarify whether adding E(2) to standard luteal P supplementation is beneficial both in GnRH agonist and antagonist IVF cycles. Meta-analysis of nine randomized controlled trials. University hospital center for reproductive medicine and IVF. None. Clinical pregnancy rate (PR) per patient, clinical PR per embryo transfer (ET), implantation rate, ongoing PR per patient, clinical abortion rate, and ectopic PR. There were no statistically significant differences between E(2)+P versus P-only group regarding overall IVF outcomes. From seven studies including GnRH agonist cycles, no statistical significant differences were found between the two groups in clinical PR per patient (relative risk [RR] 1.32, 95% confidence interval [CI] 0.79-2.19), clinical PR per ET (RR 1.83, 95% CI 0.96-3.49), implantation rate (RR 1.20, 95% CI 0.34-4.21), ongoing PR per patient (RR 1.34, 95% CI 0.37-4.82), clinical abortion rate (RR 1.05, 95% CI 0.48-2.28), and ectopic PR (RR 0.53, 95% CI 0.07-4.10). Clinical PR per patient (RR 0.94, 95% CI 0.62-1.42) and ongoing PR per patient (RR 1.09, 95% CI 0.79-1.50) from three studies including GnRH antagonist cycles only were all similar between the two groups. The combined data presented in this meta-analysis suggest that the addition of E(2) to P for luteal phase support does not improve IVF outcomes in GnRH agonist and antagonist cycles. However, the authors feel that there is an obvious need for further large-scale studies regarding GnRH antagonist cycles.

Qualité ovocytaire et embryonnaire et issue des cycles d’ICSI chez les patientes porteuses d’un syndrome des ovaires polykystiques (SOPK) versus normo-ovulantes

To compare the oocyte and embryo quality and outcomes in polycystic ovary syndrome (PCOS) patients and normo-ovulatory women undergoing intracytoplasmic sperm injection (ICSI) cycles. We studied retrospectively 100 controlled ovarian stimulation cycles for ICSI in women with PCOS and 200 cycles in normo-ovulatory women. Every PCOS woman was paired according to age with two normo-ovulatory woman undergoing ICSI during the same study period. A long protocol of gonadotrophin releasing hormone (GNRH) agonist was carried out in all patients. The main outcome measures evaluated were: cancellation of the cycles, number of aspirated follicles, oocyte maturity, fertilization rate, embryo quality pregnancy and implantation rates, clinical abortion rate, multiple pregnancy rate and the "take-home baby" rate. Khi(2) test and Student t test were used for differences between normo-ovulatory and PCOS patients and the limit of significance was set at p<0,05. ICSI was performed for male infertility in most cases (79% in PCOS group vs 79,5%; NS). There was no significant difference in term of cancellation rate (5,5% in PCOS group vs 5%; NS). The mean number of follicles was higher in patients with PCOS (18,1+/-8,5 vs 9,4+/-5,5; p<0,001). Oocyte mature rate (67% vs 52%; p<0,001), fertilization rate (75% vs 63,7%; p<0,001) and grade 1 embryo rate (69% vs 53%; p<0,001) were significantly higher in PCOS group. The mean number of transferred embryos was similar in the two groups (2,46+/-0,5 vs 2,54+/-1,01; NS). Implantation rate (16,6% vs 12,1%; NS), clinical pregnancy rate per transfer (31,5% vs 24%; NS) and Live birth rate (22% vs 20%; NS) did not differ statistically in the two groups. Twin and triplet pregnancies rates were similar in the two groups (20% vs 16,7%; NS and 6,6% vs 7,1% ; NS respectively). Miscarriage rate was higher in PCOS group but this did not reach the statistical significance (26,6% vs 16,6%; NS). PCOS patients showed better global oocyte and embryo quality. However, pregnancy and live birth rates were similar in the two groups when number and quality of transferred embryos are equivalent.

Efficacy of recombinant versus human derived follicle stimulating hormone on the oocyte and embryo quality in IVF-ICSI cycles: Randomised, controlled, multi-centre trial

The aim of this trial, comparing human follicle stimulating hormone (hFSH) and recombinant FSH (rFSH) was to evaluate the efficacy on oocyte and embryo quality in in vitro fertilisation/intracytoplasmic sperm injection cycles. Four-hundred and one women were randomised in two groups to receive or hFSH or rFSH in stimulation protocols. The primary end point of this study was the oocyte/embryo quality. No significant difference in oocyte/embryo quality was observed between the two groups. The number of oocytes retrieved was significantly higher in the hFSH group (6 ± 2.8 in hFSH group vs. 5 ± 2.6 in rFSH group; P = 0.003). A less amounts of gonadotropins consumed (2106 ± 719 IU in hFSH group vs. 3536 ± 1099 IU in rFSH group; P < 0.0001) and shorter duration of stimulation (human chorionic gonadotropin day of administration: Day 12.3 ± 1.0 in hFSH and Day 13.3 ± 1.2 in rFSH group, respectively; P < 0.0001) was registered in hFSH group. Fertilisation, cleavage and implantation rates, pregnancy and abortion rates were similar in both groups. However, lower clinical abortion rate (not significant) in hFSH group might be noteworthy. In our study, we demonstrated that hFSH and rFSH products are equivalent in terms of clinical efficacy.

Comparison of short 7-day and long gonadotropin -releasing hormone agonist protocols in the controlled ovarian stimulation for in vitro fertilization

OBJECTIVE: To compare the effects on controlled ovarian stimulation and pregrancy outcomes of a short 7-day gonadotropin-releasing hormone agonist (GnRHa) protocol(7-day protocol)and a GnRHa long protocol (long protocol) as part of controlled ovarian stimulation regimens during in vitro fertilization and embroy transfer (IVF-ET) treatment. DESIGN: Prospective randomized controlled study. MATERIALS AND METHODS: One hundred and forty six infertile patients with tubal factor who accepted IVF-ET treatment from July to November 2007 were included in this study. 7-day protocol group (n=68): GnRHa (decapeptyl, Ferring) was injected 0.1 mg daily from day 2 of the menstrual cycle to day 8. At the same time gonadotropin (Gn) was injected daily from day 3. Long protocol group(n=78): GnRHa (diphereline, Ferring)was injected 1.88 mg singly in the mid-luteal phase of previous menstrual cycle. Once the patient was down regulated, gonadotropin injection was started. On the day of human chorionic gonadotrophin (hCG) injection, serum luteinizing hormone (LH), estradiol (E2) and progesterone (P) were measured by electrochemiluminescence immunoassay. RESULTS: The level of serum progesterone on the day of hCG injection was lower in the 7-day protocol group comparing with the long protocol group (0.58±0.51ng/ml vs 0.83±0.54ng/ml, P< 0.05).There were no significant differences in the levels of serum LH, E2, E2 per oocyte and E2 per mature follicle on the day of hCG injection. Patients in the 7-day protocol group were stimulated for a shorter period (8.97±1.45 d vs 11.41±1.43 d, P< 0.05), injected fewer Gn ampoules (1851.65±616.96 IU vs 2726.44±769.28 IU, P< 0.05),comparing with patients in the long protocol group. When comparing the results in the numbers of oocytes retrieved (14.74±6.72 vs 16.47±8.90), fertilization rate (77.94% vs 77.74%), cleaved embryos rate (94.11% vs 96.10%), top-quality embryos rate (60.68% vs 58.85%), implantation rate (25% vs 33.12%), pregnancy rate (50.00% vs 52.56%) and clinical abortion rate (5.88% vs 14.34%), the 7-day protocol group was similar to those of the long protocol group (P >0.05). CONCLUSIONS: The short 7-day GnRHa protocol and GnRHa long protocol had equal effects on controlled ovarian stimulation and pregrancy outcomes for in vitro fertilization and embroy transfer treatment. Patients who received the short 7-day GnRHa protocol required fewer ampoules of gonadotropin and shorter periods of treatment than those who received the GnRHa long protocol.

Comparison of follicular fluid insulin-like growth factor II and insulin-like growth factor binding protein 4 levels between short 7-day and long gonadotropin-releasing hormone agonist protocols

OBJECTIVE: Insulin-like growth factor II (IGF-II) and Insulin-like growth factor binding protein 4 (IGFBP-4) play a major role in the autocrine and paracrine regulation of folliculogenesis. To explore the individual influence on the intrafollicular microenvironment between the short 7-day gonadotropin-releasing hormone agonist (GnRHa) protocol (7-day protocol) and GnRHa long protocol (long protocol) by comparing the concentrations of IGF-II, IGFBP-4, and the ratio of IGF-II/IGFBP-4 in follicular fluid. DESIGN: Prospective randomized controlled study. MATERIALS AND METHODS: 88 infertile patients with tubal factor who accepted IVF treatment from July to October 2007 were included in this study. 7-day protocol group (n=44): GnRHa (decapeptyl, Ferring) was injected 0.1 mg daily from day 2 of the menstrual cycle to day 8. At the same time gonadotropin (Gn) was injected daily from day 3. Long protocol group (n=44): GnRHa (diphereline, Ferring) was injected 1.88 mg singly in the mid-luteal phase of previous menstrual cycle. Once the patient was down regulated, gonadotropin injection was started. Follicular fluid was obtained from dominant follicles during oocyte retrieval. The levels of IGF-II and IGFBP-4 in follicular fluid were detected separately by radioimmunoassay and enzyme-linked immunosorbent assay. RESULTS: The durations of controlled ovarian stimulation was significantly shorter and total dose of Gn used were significantly lower in the 7-day protocol group. The levels of serum E2 and E2 per mature follicle on the day of hCG injection, the number of oocytes retrieved, fertilization rate, cleaved embryos rate, top-quality embryos rate, implantation rate, pregnancy rate, and clinical abortion rate were similar between the two groups. The concentrations of IGF-II (0.17±0.06ng/ml vs 0.20±0.07 ng/ml, P=0.020) and IGFBP-4 (2915.48±1443.02pg/ml vs 3646.64±1818.67pg/ml, P=0.040) in follicular fluid of the 7-day protocol group patients were significantly lower. There was no significant difference in the ratio of IGF-II/IGFBP-4 (0.07±0.04 vs 0.07±0.03, P=0.471) between the 7-day and long protocol group. Linear correlation analysis showed that the level of follicular fluid IGF-II was positively correlated to total dose of Gn used (r=0.316, P <0.05). CONCLUSIONS: The short 7-day and long GnRHa protocols may affect the concentrations of follicular fluid IGF-II and IGFBP-4. However, the changes of follicular fluid IGF-II and IGFBP-4 concentrations may not contribute to different clinical outcomes.

Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome

Frozen embryo transfers are characterized by impaired pregnancy outcome and increased incidence of pregnancy loss as compared with fresh IVF/ICSI embryo transfers. In this study, we performed a retrospective analysis of clinical and embryological factors that potentially influence the outcome of frozen embryo transfer. We reviewed the outcome of 1242 frozen embryo transfers with respect to the age of the woman, the method of fertilization, embryo quality before and after freezing and the number of embryos transferred. The pregnancy (positive hCG) and clinical pregnancy rates were 25.8 and 21.1%, respectively. A total of 107 (33.3%) of the 321 pregnancies identified by a positive hCG test miscarried either before (18.4%) or after (15%) the clinical recognition of gestational sac(s). The delivery rate for the frozen embryo transfers analysed was 17.2%. Our data revealed that the delivery rate after frozen embryo transfer was dependent on both the woman's age and the quality of embryos transferred, at the same time being unaffected by IVF/ICSI treatment. In addition, the increased woman's age at IVF/ICSI treatment was identified as the only parameter elevating the biochemical pregnancy rate, whereas the clinical abortion rate was found to be unrelated to the clinical or embryological parameters studied.